25 results on '"Schmook MT"'
Search Results
2. Plasmapheresis and Cyclophosphamide therapy in an eight year old girl with cerebral manifestation of systemic lupus erythematodes
- Author
-
Ulbrich, A, primary, Lanator, I, additional, Csaicsich, D, additional, Schmook, MT, additional, Seidl, R, additional, and Emminger, W, additional
- Published
- 2011
- Full Text
- View/download PDF
3. Early plasmapheresis in 3 consecutive cases of choreo-athetotic movement disorder after HSV-1 encephalitis
- Author
-
Lanator, I, primary, Freilinger, M, additional, Csaicsich, D, additional, Seidl, R, additional, and Schmook, MT, additional
- Published
- 2011
- Full Text
- View/download PDF
4. CT-MR image data fusion for computer-assisted navigated surgery of orbital tumors.
- Author
-
Nemec SF, Peloschek P, Schmook MT, Krestan CR, Hauff W, Matula C, and Czerny C
- Published
- 2010
- Full Text
- View/download PDF
5. Alternative lengthening of telomere-based immortalization renders H3G34R -mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.
- Author
-
Laemmerer A, Lehmann C, Mayr L, Bruckner K, Gabler L, Senfter D, Meyer P, Balber T, Pirker C, Jaunecker CN, Kirchhofer D, Vician P, Griesser M, Spiegl-Kreinecker S, Schmook MT, Traub-Weidinger T, Kuess P, Eckert F, Federico A, Madlener S, Stepien N, Robl B, Baumgartner A, Hainfellner JA, Dieckmann K, Dorfer C, Roessler K, Corsini NS, Holzmann K, Schmidt WM, Peyrl A, Azizi AA, Haberler C, Beck A, Pfister SM, Schueler J, Loetsch-Gojo D, Knoblich JA, Berger W, and Gojo J
- Abstract
Background: Diffuse hemispheric glioma, H3G34R/V-mutant (DHG-H3G34) is characterized by poor prognosis and lack of effective treatment options. DHG-H3G34R further harbor deactivation of Alpha-Thalassemia/Mental Retardation Syndrome X-linked protein (ATRX; DHG-H3G34R_ATRX) suggesting a unique interaction of these two oncogenic alterations. In this study, we dissect their cell biological interplay, investigate the impact on telomere stabilization and, consequently, validate a targeted therapy approach., Methods: We characterized patient-derived primary pediatric high-grade glioma (pHGG) models for telomere-maintenance mechanisms, DNA damage stress (including protein expression, pH2AX/Rad51 foci, cell-cycle arrest) and their sensitivity towards poly-ADP polymerase inhibitor (PARPi) combinations. Human induced pluripotent stem cells (iPSCs) were used for modelling the disease. The anticancer activity of PARPi combinations in vivo was studied in Chorioallantoic Membrane (CAM) and orthotopic in vivo experiments. Finally, we treated a DHG-H3G34R_ATRX patient with a PARPi combination therapy., Results: We elaborate that alternative lengthening of telomeres (ALT) is a key characteristic of DHG-H3G34R_ATRX. A dominant cooperative effect between H3G34R and ATRX loss in ALT activation also became apparent in iPSCs, which endogenously exert telomerase activity. In both, patient-derived DHG-H3G34R_ATRX models and H3G34R+/ATRX- iPSCs, the ALT phenotype was associated with increased basal DNA damage stress, mediating synergistic susceptibility towards PARPi (talazoparib, niraparib) combinations with topoisomerase-I inhibitors (topotecan, irinotecan). In a first-of-its-kind case, treatment of a DHG-H3G34R_ATRX patient with the brain-penetrant PARP inhibitor niraparib and topotecan resulted in a significant tumor reduction., Conclusion: Our preclinical and clinical data strongly support the further development of PARPis together with DNA damage stress-inducing treatment regimens for DHG-H3G34R_ATRX., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
6. Pearls & Oy-sters: Neurologic Involvement in Shiga Toxin-Associated Hemolytic Uremic Syndrome.
- Author
-
Fodor TA, Schmook MT, and Brücke C
- Subjects
- Humans, Female, Middle Aged, Shiga-Toxigenic Escherichia coli pathogenicity, Escherichia coli Infections complications, Hemolytic-Uremic Syndrome complications
- Abstract
Shiga toxin-producing Escherichia coli (STEC) is among the most common pathogens that cause bacterial enteritis. They can also lead to extraintestinal manifestations including hemolytic uremic syndrome (HUS), which is defined by the triad of hemolytic anemia, thrombocytopenia, and acute renal dysfunction due to Shiga toxin-mediated damage to the vascular endothelium with a subsequent inflammatory reaction and thrombotic microangiopathy. The thrombotic microangiopathy mainly affects the small blood vessels of the kidneys and brain. Neurologic involvement, especially in adults, is rare but can include nonspecific symptoms such as a decreased consciousness, altered mental status, seizures, and hyperreflexia. Although HUS is often assumed to cause isolated involvement of small vessels, in this case report, a 52-year-old woman with a STEC-HUS-encephalopathy developed multiple craniocervical dissections during the course of her disease in the absence of any trauma or cardiovascular risk factors. This case thus could possibly indicate that Shiga toxin-mediated damages are not limited to the small vessels but can also affect larger vessels.
- Published
- 2024
- Full Text
- View/download PDF
7. Developmental, Cognitive, Ocular Motor, and Neuroimaging Findings Related to SUFU Haploinsufficiency: Unraveling Subtle and Highly Variable Phenotypes.
- Author
-
Siegert S, Grisold A, Pal-Handl K, Lilja S, Kepa S, Silvaieh S, Laccone F, Wiest G, Pogledic I, Schmook MT, Boltshauser E, Schmidt WM, and Krenn M
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Male, Abnormalities, Multiple genetics, Abnormalities, Multiple diagnostic imaging, Abnormalities, Multiple physiopathology, Apraxias diagnostic imaging, Apraxias genetics, Apraxias physiopathology, Apraxias congenital, Cerebellum diagnostic imaging, Cerebellum abnormalities, Cogan Syndrome, Eye Abnormalities genetics, Eye Abnormalities diagnostic imaging, Kidney Diseases, Cystic genetics, Kidney Diseases, Cystic diagnostic imaging, Neuroimaging, Retina diagnostic imaging, Retina abnormalities, Repressor Proteins genetics, Repressor Proteins metabolism, Developmental Disabilities diagnostic imaging, Developmental Disabilities genetics, Developmental Disabilities etiology, Developmental Disabilities physiopathology, Haploinsufficiency, Phenotype
- Abstract
Background: Biallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency., Methods: Nine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing., Results: We identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals., Conclusions: Our data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
8. Feasibility and antitumour activity of the FGFR inhibitor erdafitnib in three paediatric CNS tumour patients.
- Author
-
Stepien N, Mayr L, Schmook MT, Raimann A, Dorfer C, Peyrl A, Azizi AA, Schramm K, Haberler C, and Gojo J
- Subjects
- Child, Humans, Feasibility Studies, Signal Transduction, Glioma drug therapy, Glioma genetics, Glioma pathology, Brain Neoplasms drug therapy
- Abstract
Alterations of the fibroblast growth factor (FGF) signalling pathway are increasingly recognized as frequent oncogenic drivers of paediatric brain tumours. We report on three patients treated with the selective FGFR1-4 inhibitor erdafitinib. Two patients were diagnosed with a posterior fossa ependymoma group A (PFA EPN) and one with a low-grade glioma (LGG), harbouring FGFR3/FGFR1 overexpression and an FGFR1 internal tandem duplication (ITD), respectively. While both EPN patients did not respond to erdafitinib treatment, the FGFR1-ITD-harbouring tumour showed a significant decrease in tumour volume and contrast enhancement throughout treatment. The tumour remained stable 6 months after treatment discontinuation., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
9. Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen: A Nonrandomized Controlled Trial.
- Author
-
Peyrl A, Chocholous M, Sabel M, Lassaletta A, Sterba J, Leblond P, Nysom K, Torsvik I, Chi SN, Perwein T, Jones N, Holm S, Nyman P, Mörse H, Öberg A, Weiler-Wichtl L, Leiss U, Haberler C, Schmook MT, Mayr L, Dieckmann K, Kool M, Gojo J, Azizi AA, André N, Kieran M, and Slavc I
- Subjects
- Humans, Male, Child, Child, Preschool, Adolescent, Female, Etoposide, Quality of Life, Administration, Metronomic, Antineoplastic Combined Chemotherapy Protocols adverse effects, Medulloblastoma drug therapy, Medulloblastoma etiology, Brain Neoplasms drug therapy, Cerebellar Neoplasms drug therapy, Cerebellar Neoplasms etiology
- Abstract
Importance: Medulloblastoma recurrence in patients who have previously received irradiation has a dismal prognosis and lacks a standard salvage regimen., Objective: To evaluate the response rate of pediatric patients with medulloblastoma recurrence using an antiangiogenic metronomic combinatorial approach (Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial [MEMMAT])., Design, Setting, and Participants: This phase 2, investigator-initiated, multicenter nonrandomized controlled trial assessed 40 patients with relapsed or refractory medulloblastoma without a ventriculoperitoneal shunt who were younger than 20 years at original diagnosis. Patients were enrolled between April 1, 2014, and March 31, 2021., Interventions: Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose (metronomic) oral etoposide and cyclophosphamide, supplemented by intravenous bevacizumab and intraventricular therapy consisting of alternating etoposide and cytarabine., Main Outcomes and Measures: The primary end point was response after 6 months of antiangiogenic metronomic therapy. Secondary end points included progression-free survival (PFS), overall survival (OS), and quality of life. Adverse events were monitored to assess safety., Results: Of the 40 patients (median [range] age at treatment start, 10 [4-17] years; 25 [62.5%] male) prospectively enrolled, 23 (57.5%) achieved disease control after 6 months of treatment, with a response detected in 18 patients (45.0%). Median OS was 25.5 months (range, 10.9-40.0 months), and median PFS was 8.5 months (range, 1.7-15.4 months). Mean (SD) PFS at both 3 and 5 years was 24.6% (7.9%), while mean (SD) OS at 3 and 5 years was 43.6% (8.5%) and 22.6% (8.8%), respectively. No significant differences in PFS or OS were evident based on molecular subgroup analysis or the number of prior recurrences. In patients demonstrating a response, mean (SD) overall 5-year PFS was 49.7% (14.3%), and for patients who remained progression free for the first 12 months of treatment, mean (SD) 5-year PFS was 66.7% (16.1%). Treatment was generally well tolerated. Grade 3 to 4 treatment-related adverse events included myelosuppression, infections, seizures, and headaches. One heavily pretreated patient with a third recurrence died of secondary acute myeloid leukemia., Conclusions and Relevance: This feasible and well-tolerated MEMMAT combination regimen demonstrated promising activity in patients with previously irradiated recurrent medulloblastoma. Given these results, this predominantly oral, well-tolerated, and outpatient treatment warrants further evaluation., Trial Registration: ClinicalTrials.gov Identifier: NCT01356290.
- Published
- 2023
- Full Text
- View/download PDF
10. Unique Finding of a Primary Central Nervous System Neuroendocrine Carcinoma in a 5-Year-Old Child: A Case Report.
- Author
-
Stepien N, Haberler C, Theurer S, Schmook MT, Lütgendorf-Caucig C, Müllauer L, Gojo J, Azizi AA, Czech T, Slavc I, and Peyrl A
- Abstract
Neuroendocrine tumors (NETs) are rare neoplasms predominantly arising in the gastrointestinal-tract or the lungs of adults. To date, only ten cases of primary central nervous system (CNS) NETs have been reported, with just three of them describing a neuroendocrine carcinoma (NECA) and none occurring in a child. We report on a previously healthy 5-year-old boy, who presented with headaches, nausea and vomiting, and was diagnosed with a left cerebellar solid mass with a cystic component. After gross-total resection, histology revealed a neuroendocrine carcinoma. Molecular analysis of the tumor tissue showed a KRAS -splice-site mutation (c451-3C > T). The KRAS -mutation was discovered to be a maternal germline mutation, previously described as likely benign. After extensive search for an extracranial primary tumor, including Ga-68 DOTANOC-PET-CT, the diagnosis of a primary CNS NECA was established, and proton irradiation was performed. Unfortunately, the patient developed an in-field recurrence just 5 weeks after the end of radiotherapy. The tumor was re-resected with vital tumor tissue. Six cycles of chemotherapy were initiated, consisting of cisplatin, carboplatin, etoposide and ifosfamide. The patient remains disease free 22 months after the end of treatment, supporting the beneficial effect of platinum- and etoposide-based chemotherapy for this tumor entity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Stepien, Haberler, Theurer, Schmook, Lütgendorf-Caucig, Müllauer, Gojo, Azizi, Czech, Slavc and Peyrl.)
- Published
- 2022
- Full Text
- View/download PDF
11. Targeting fibroblast growth factor receptors to combat aggressive ependymoma.
- Author
-
Lötsch D, Kirchhofer D, Englinger B, Jiang L, Okonechnikov K, Senfter D, Laemmerer A, Gabler L, Pirker C, Donson AM, Bannauer P, Korbel P, Jaunecker CN, Hübner JM, Mayr L, Madlener S, Schmook MT, Ricken G, Maaß K, Grusch M, Holzmann K, Grasl-Kraupp B, Spiegl-Kreinecker S, Hsu J, Dorfer C, Rössler K, Azizi AA, Foreman NK, Peyrl A, Haberler C, Czech T, Slavc I, Filbin MG, Pajtler KW, Kool M, Berger W, and Gojo J
- Subjects
- Animals, Central Nervous System Neoplasms genetics, Central Nervous System Neoplasms pathology, Ependymoma genetics, Humans, Mice, Neoplasm Recurrence, Local metabolism, Receptor, Fibroblast Growth Factor, Type 1 genetics, Receptor, Fibroblast Growth Factor, Type 1 metabolism, Receptor, Fibroblast Growth Factor, Type 3 metabolism, Receptors, Fibroblast Growth Factor genetics, Ependymoma pathology, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Receptors, Fibroblast Growth Factor metabolism
- Abstract
Ependymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
12. Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis.
- Author
-
Baumgartner A, Stepien N, Mayr L, Madlener S, Dorfer C, Schmook MT, Traub-Weidinger T, Lötsch-Gojo D, Kirchhofer D, Reisinger D, Hedrich C, Arshad S, Irschik S, Boztug H, Engstler G, Bernkopf M, Rifatbegovic F, Höller C, Slavc I, Berger W, Müllauer L, Haberler C, Azizi AA, Peyrl A, and Gojo J
- Abstract
Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of NRAS ( n = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type.
- Published
- 2021
- Full Text
- View/download PDF
13. Influence of socioeconomic status on cognitive outcome after childhood arterial ischemic stroke.
- Author
-
Bartha-Doering L, Gleiss A, Knaus S, Schmook MT, and Seidl R
- Subjects
- Adolescent, Child, Cognition physiology, Cognition Disorders psychology, Female, Humans, Ischemic Stroke psychology, Language, Male, Social Class, Socioeconomic Factors, Attention physiology, Cognition Disorders etiology, Executive Function physiology, Ischemic Stroke complications, Memory physiology, Problem Solving physiology
- Abstract
Aim: To determine whether socioeconomic status (SES) is a stronger predictor for cognitive outcome after childhood arterial ischemic stroke compared to clinical factors., Method: We investigated perceptual reasoning, executive functions, language, memory, and attention in 18 children and adolescents (12 males, six females, median age at testing 13y 4mo, range 7y-17y 5mo) after arterial ischemic stroke; collected sociodemographic information (education of parents, household income); and used clinical information (initial lesion volume, residual lesion volume, age at stroke, time since stroke). Linear regression models were used to investigate the potential influence of SES and clinical parameters on cognitive abilities., Results: SES had a moderate effect on all cognitive outcome parameters except attention by explaining 41.9%, 37.9%, 38.0%, and 22.5% of variability in perceptual reasoning, executive functions, language, and memory respectively. Initial lesion volume was the only clinical parameter that showed moderate importance on cognitive outcome (33.1% and 25.6% of the variability in perceptual reasoning and memory respectively). Overall, SES was a stronger predictor of cognitive outcome than clinical factors., Interpretation: Future paediatric studies aiming at clinical predictors of cognitive outcome should control their analyses for SES in their study participants. The findings of the present study further point to the need for more attention to the treatment of children with low SES., What This Paper Adds: Socioeconomic status (SES) explains up to 42% of variance in cognitive outcome after childhood arterial ischemic stroke. SES is a stronger predictor of outcome than clinical factors., (© 2020 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)
- Published
- 2021
- Full Text
- View/download PDF
14. Cerebrospinal Fluid Penetration and Combination Therapy of Entrectinib for Disseminated ROS1/NTRK -Fusion Positive Pediatric High-Grade Glioma.
- Author
-
Mayr L, Guntner AS, Madlener S, Schmook MT, Peyrl A, Azizi AA, Dieckmann K, Reisinger D, Stepien NM, Schramm K, Laemmerer A, Jones DTW, Ecker J, Sahm F, Milde T, Pajtler KW, Blattner-Johnson M, Strbac M, Dorfer C, Czech T, Kirchhofer D, Gabler L, Berger W, Haberler C, Müllauer L, Buchberger W, Slavc I, Lötsch-Gojo D, and Gojo J
- Abstract
Targeting oncogenic fusion-genes in pediatric high-grade gliomas (pHGG) with entrectinib has emerged as a highly promising therapeutic approach. Despite ongoing clinical studies, to date, no reports on the treatment of cerebrospinal fluid (CSF) disseminated fusion-positive pHGG exist. Moreover, clinically important information of combination with other treatment modalities such as intrathecal therapy, radiotherapy and other targeted agents is missing. We report on our clinical experience of entrectinib therapy in two CSF disseminated ROS1/NTRK -fusion-positive pHGG cases. Combination of entrectinib with radiotherapy or intrathecal chemotherapy appears to be safe and has the potential to act synergistically with entrectinib treatment. In addition, we demonstrate CSF penetrance of entrectinib for the first time in patient samples suggesting target engagement even upon CSF dissemination. Moreover, in vitro analyses of two novel cell models derived from one case with NTRK -fusion revealed that combination therapy with either a MEK (trametinib) or a CDK4/6 (abemaciclib) inhibitor synergistically enhances entrectinib anticancer effects. In summary, our comprehensive study, including clinical experience, CSF penetrance and in vitro data on entrectinib therapy of NTRK/ROS1 -fusion-positive pHGG, provides essential clinical and preclinical insights into the multimodal treatment of these highly aggressive tumors. Our data suggest that combined inhibition of NTRK/ROS1 and other therapeutic vulnerabilities enhances the antitumor effect, which should be followed-up in further preclinical and clinical studies.
- Published
- 2020
- Full Text
- View/download PDF
15. An adolescent with herpes simplex encephalitis, presenting with mild symptoms and rapid deterioration: A case report.
- Author
-
Stepien N, Weseslindtner L, Seidl R, Geldner J, Golej J, Schmook MT, and Peyrl A
- Abstract
Headaches in children are a common, but unspecific symptom that can have many underlying causes, ranging from unspecific tension headache through migraine and up to encephalitis and intracranial hypertension. We present the case of a 14-year-old boy who presented to our emergency department with headache, nausea as well as vomiting and developed seizures later on. The initial diagnosis was complicated by a magnetic resonance imaging which did not show any signs of inflammation, but was of limited informative value due to orthodontic appliances. Despite the unremarkable imaging, prophylactic antiviral and antibiotic treatment was started after lumbar puncture. Herpes simplex virus as well as human herpes virus 7 were confirmed in the cerebrospinal fluid. Although both viruses are ubiquitous, severe infections are a rare complication. Immunodeficiency syndromes are predisposing factors for serious complications and genetic analysis of UNC93B and TLR-3 might be helpful for decision-making. No genetic or immunologic predisposition was found in our patient. The patient's condition deteriorated rapidly, so he had to be admitted to the pediatric intensive care unit, where he was intubated and his antiviral treatment with acyclovir was extended by foscarnet. After prolonged mechanical ventilation, he slowly improved. With intensive neurorehabilitation, he could finally return to his daily life activities 3 months after diagnosis. Despite headaches being an unspecific symptom, the possibility of a herpes simplex virus encephalitis should always kept in mind, especially in patients presenting with additional symptoms such as vomiting, altered mental status and/or focal neurological deficits. An initial magnetic resonance imaging might be misleading if orthodontic appliances are in place. Initiation of treatment without delay is crucial for neurologic outcome of herpes simplex virus encephalitis., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2020.)
- Published
- 2020
- Full Text
- View/download PDF
16. Personalized Treatment of H3K27M-Mutant Pediatric Diffuse Gliomas Provides Improved Therapeutic Opportunities.
- Author
-
Gojo J, Pavelka Z, Zapletalova D, Schmook MT, Mayr L, Madlener S, Kyr M, Vejmelkova K, Smrcka M, Czech T, Dorfer C, Skotakova J, Azizi AA, Chocholous M, Reisinger D, Lastovicka D, Valik D, Haberler C, Peyrl A, Noskova H, Pál K, Jezova M, Veselska R, Kozakova S, Slaby O, Slavc I, and Sterba J
- Abstract
Diffuse gliomas with K27M histone mutations (H3K27M glioma) are generally characterized by a fatal prognosis, particularly affecting the pediatric population. Based on the molecular heterogeneity observed in this tumor type, personalized treatment is considered to substantially improve therapeutic options. Therefore, clinical evidence for therapy, guided by comprehensive molecular profiling, is urgently required. In this study, we analyzed feasibility and clinical outcomes in a cohort of 12 H3K27M glioma cases treated at two centers. Patients were subjected to personalized treatment either at primary diagnosis or disease progression and received backbone therapy including focal irradiation. Molecular analyses included whole-exome sequencing of tumor and germline DNA, RNA-sequencing, and transcriptomic profiling. Patients were monitored with regular clinical as well as radiological follow-up. In one case, liquid biopsy of cerebrospinal fluid (CSF) was used. Analyses could be completed in 83% (10/12) and subsequent personalized treatment for one or more additional pharmacological therapies could be recommended in 90% (9/10). Personalized treatment included inhibition of the PI3K/AKT/mTOR pathway (3/9), MAPK signaling (2/9), immunotherapy (2/9), receptor tyrosine kinase inhibition (2/9), and retinoic receptor agonist (1/9). The overall response rate within the cohort was 78% (7/9) including one complete remission, three partial responses, and three stable diseases. Sustained responses lasting for 28 to 150 weeks were observed for cases with PIK3CA mutations treated with either miltefosine or everolimus and additional treatment with trametinib/dabrafenib in a case with BRAFV600E mutation. Immune checkpoint inhibitor treatment of a case with increased tumor mutational burden (TMB) resulted in complete remission lasting 40 weeks. Median time to progression was 29 weeks. Median overall survival (OS) in the personalized treatment cohort was 16.5 months. Last, we compared OS to a control cohort ( n = 9) showing a median OS of 17.5 months. No significant difference between the cohorts could be detected, but long-term survivors (>2 years) were only present in the personalized treatment cohort. Taken together, we present the first evidence of clinical efficacy and an improved patient outcome through a personalized approach at least in selected cases of H3K27M glioma., (Copyright © 2020 Gojo, Pavelka, Zapletalova, Schmook, Mayr, Madlener, Kyr, Vejmelkova, Smrcka, Czech, Dorfer, Skotakova, Azizi, Chocholous, Reisinger, Lastovicka, Valik, Haberler, Peyrl, Noskova, Pál, Jezova, Veselska, Kozakova, Slaby, Slavc and Sterba.)
- Published
- 2020
- Full Text
- View/download PDF
17. Hand MRI and the Greulich-Pyle atlas in skeletal age estimation in adolescents.
- Author
-
Hojreh A, Gamper J, Schmook MT, Weber M, Prayer D, Herold CJ, and Noebauer-Huhmann IM
- Subjects
- Adolescent, Female, Humans, Male, Age Determination by Skeleton methods, Atlases as Topic, Hand diagnostic imaging, Magnetic Resonance Imaging methods
- Abstract
Objective: To evaluate the feasibility of hand MRI in age assessment in adolescents using the Greulich-Pyle (GP) atlas criteria., Materials and Methods: Two radiologists, who were blinded to the study subjects' chronologic ages, semi-objectively evaluated 1.5-T MRIs of the left hands of ten patients (13.5 ± 2.6 years) who had left-hand radiographs and 50 healthy volunteers (15 ± 2 years)., Results: A coronal T1-weighted, volumetric, interpolated, breath-hold examination with water excitation (T1 VIBE-3D-WE) achieved the best image quality. The correlation between estimated patients' ages on radiographs and MRI was high. The average estimated age difference between the MRIs and radiographs was -0.05 years for reader 1 and -0.175 years for reader 2. The interclass coefficients (ICCs) showed high interobserver agreement (radiographs: ICC = 0.95, MRI: ICC = 0.97). The ICC, calculated separately for the male and female volunteers' estimated ages by MRI, also showed a high agreement between the two readers (male: ICC = 0.97, female: ICC = 0.95). Reader 1 estimated 94% of volunteers within 2 standard deviations (SD) and 62% within 1 SD. The results for reader 2 were 92% and 54%, respectively. Thirty-nine percent of girls and 27% of boys were estimated to be older using 1 SD., Conclusion: MRI of the left hand is a feasible alternative to hand radiographs for skeletal age estimation in adolescents using the GP criteria with 2 SD. Using 1 SD, the age of healthy volunteers tended to be estimated as higher than the chronologic age. Future studies should evaluate the results in a larger number of participants.
- Published
- 2018
- Full Text
- View/download PDF
18. Childhood onset temporal lobe epilepsy: Beyond hippocampal sclerosis.
- Author
-
Mühlebner A, Breu M, Kasprian G, Schmook MT, Stefanits H, Scholl T, Samueli S, Gröppel G, Dressler A, Prayer D, Czech T, Hainfellner JA, and Feucht M
- Subjects
- Adolescent, Child, Child, Preschool, Drug Resistant Epilepsy physiopathology, Epilepsy, Temporal Lobe physiopathology, Female, Humans, Magnetic Resonance Imaging, Male, Malformations of Cortical Development pathology, Phenotype, Sclerosis, Seizures, Febrile complications, Drug Resistant Epilepsy etiology, Epilepsy, Temporal Lobe etiology, Hippocampus pathology, Malformations of Cortical Development complications
- Abstract
Objective: Hippocampal Sclerosis (HS) is widely recognized as a significant underlying cause of drug-resistant temporal lobe epilepsy (TLE) in adults. In contrast, HS is a rare finding in pediatric surgical series, and a higher incidence of HS associated with cortical dysplasia (i.e. FCD type IIIa according to the new ILAE classification) than in adult series has been reported. Data about the electro-clinical characteristics of this subgroup are scarce., Methods: We studied 15 children and adolescents with drug-resistant TLE and HS who had anterior temporal lobe resection at our center with regard to electroclinical characteristics, MRI features and histopathology. Children in whom histopathology was consistent with Focal Cortical Dysplasia (FCD) type IIIa (n = 7) were compared with those who had HS only (n = 8)., Results: Clinical characteristics associated with this highly selective subset of patients with FCD type IIIa were: the presence of febrile seizures during infancy, a shorter duration of active epilepsy and a lower age at epilepsy surgery. In addition, there were non-significant trends towards more extended abnormalities on both EEG and neuroimaging. We were, however, not able to find group differences with respect to neuropathologic subtyping of the HS., Conclusion: We present the first detailed description and comprehensive data analysis of children with FCD type IIIa. According to our results, this patient group seems to show a distinct clinical phenotype., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
19. MED20 mutation associated with infantile basal ganglia degeneration and brain atrophy.
- Author
-
Vodopiutz J, Schmook MT, Konstantopoulou V, Plecko B, Greber-Platzer S, Creus M, Seidl R, and Janecke AR
- Subjects
- Adolescent, Atrophy, Child, Preschool, Dystonia diagnosis, Exome genetics, Female, Genetic Linkage, Humans, Magnetic Resonance Imaging, Muscle Spasticity diagnosis, Pedigree, Basal Ganglia Diseases genetics, Brain pathology, Dystonia genetics, Mediator Complex genetics, Muscle Spasticity genetics, Mutation, Missense
- Abstract
Unlabelled: Infantile movement disorders are rare and genetically heterogeneous. We set out to identify the disease-causing mutation in siblings with a novel recessive neurodegenerative movement disorder. Genetic linkage analysis and whole-exome sequencing were performed in the original family. A cohort of six unrelated patients were sequenced for further mutations in the identified candidate gene. Pathogenicity of the mutation was evaluated by in silico analyses and by structural modeling. We identified the first and homozygous mutation (p.Gly114Ala) in the Mediator subunit 20 gene (MED20) in siblings presenting with infantile-onset spasticity and childhood-onset dystonia, progressive basal ganglia degeneration, and brain atrophy. Mediator refers to an evolutionarily conserved multi-subunit RNA polymerase II co-regulatory complex. Pathogenicity of the identified missense mutation is suggested by in silico analyses, by structural modeling, and by previous reporting of mutations in four distinct Mediator subunits causing neurodegenerative phenotypes. No further MED20 mutations were detected in this study., Conclusion: We delineate a novel infantile-onset neurodegenerative movement disorder and emphasize the Mediator complex as critical for normal neuronal function. Definitive proof of pathogenicity of the identified MED20 mutation will require confirmation in unrelated patients.
- Published
- 2015
- Full Text
- View/download PDF
20. Antiangiogenic metronomic therapy for children with recurrent embryonal brain tumors.
- Author
-
Peyrl A, Chocholous M, Kieran MW, Azizi AA, Prucker C, Czech T, Dieckmann K, Schmook MT, Haberler C, Leiss U, and Slavc I
- Subjects
- Administration, Metronomic, Antineoplastic Combined Chemotherapy Protocols adverse effects, Brain Neoplasms mortality, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Male, Neoplasms, Germ Cell and Embryonal mortality, Recurrence, Young Adult, Angiogenesis Inhibitors administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Brain Neoplasms drug therapy, Neoplasms, Germ Cell and Embryonal drug therapy
- Abstract
Background: Median survival time of recurrent embryonal brain tumors is short regardless of salvage chemotherapy used. An evolving alternative approach to conventional chemotherapy is to target neovascularization by interfering with tumor angiogenesis at various levels., Procedure: From November 2006 to December 2010, 16 patients (median age: 9 years) with recurrent (9 first, 7 multiple) embryonal brain tumors were treated with an antiangiogenic multidrug combination regimen (bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide, and cyclophophamide) and additional intraventricular therapy (etoposide and liposomal cytarabine)., Results: At a median of 33 months, 10/16 patients are alive. 4/4 patients with CNS primitive neuroectodermal tumors (CNS PNET) and 1/7 patients with medulloblastoma (MB) died of tumor progression during the first year. Another patient with MB died of an accident after 23 months, the remaining five patients with MB are alive for 12, 33, 33, 37, and 58 months. For the seven patients with MB, both overall survival (OS) and event free survival (EFS) after 6 months was 100%, after 12 months 85.7 ± 13%, and after 24 months 68.6 ± 19%. In contrast, for patients with CNS PNET, both OS and EFS after 6 months was 75.0 ± 22% and 0.0% and all patients had died by 12 months. Low-dose oral etoposide and cyclophosphamide was reduced after a median of 2 months and discontinued after a median of 11 months. Toxicities were manageable and therapy was generally well tolerated., Conclusion: Our results suggest that the chosen antiangiogenic drug combination is particularly beneficial for patients with MB and warrants further investigation., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
- View/download PDF
21. Extensive pleural and pericardial effusion in chronic myeloid leukemia during treatment with dasatinib at 100 mg or 50 mg daily.
- Author
-
Krauth MT, Herndlhofer S, Schmook MT, Mitterbauer-Hohendanner G, Schlögl E, and Valent P
- Subjects
- Adult, Aged, Dasatinib, Drug Administration Schedule, Female, Humans, Incidence, Male, Middle Aged, Risk Factors, Treatment Outcome, Antineoplastic Agents adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Pericardial Effusion chemically induced, Pleural Effusion chemically induced, Pyrimidines adverse effects, Thiazoles adverse effects
- Abstract
Dasatinib is considered an effective drug in imatinib-resistant chronic myeloid leukemia. Although reported to be well-tolerated, severe events such as pleural or pericardial effusion have been reported at 140 mg daily. We examined our chronic myeloid leukemia patients treated with dasatinib at 100 mg or 50 mg daily and identified 4 of 13 patients who developed marked effusion formation. In 2 patients, grade III/IV pleural and/or pericardial effusions were recorded. All 4 patients had received previous anti-leukemia therapy but none had pre-existing cardiac or pulmonary diseases. In 3 patients, dasatinib had to be discontinued despite treatment with diuretics and glucocorticosteroids. In conclusion, dasatinib-treated chronic myeloid leukemia patients are at risk for the development of pleural and pericardial effusions even when the drug is administered at 100 mg or 50 mg daily. Therefore, all patients should be examined for pre-existing comorbidity and risk factors before starting dasatinib and all should have repeated chest X-rays during long-term dasatinib therapy.
- Published
- 2011
- Full Text
- View/download PDF
22. Forebrain development in fetal MRI: evaluation of anatomical landmarks before gestational week 27.
- Author
-
Schmook MT, Brugger PC, Weber M, Kasprian G, Nemec S, Krampl-Bettelheim E, and Prayer D
- Subjects
- Female, Humans, Male, Models, Anatomic, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Second, Prosencephalon growth & development, Magnetic Resonance Imaging methods, Prenatal Diagnosis methods, Prosencephalon anatomy & histology, Prosencephalon embryology
- Abstract
Introduction: Forebrain malformations include some of the most severe developmental anomalies and require early diagnosis. The proof of normal or abnormal prosencephalic development may have an influence on further management in the event of a suspected fetal malformation. The purpose of this retrospective study was to evaluate the detectability of anatomical landmarks of forebrain development using in vivo fetal magnetic resonance imaging (MRI) before gestational week (gw) 27., Methods: MRI studies of 83 singleton fetuses (gw 16-26, average +/- sd: gw 22 +/- 2) performed at 1.5 Tesla were assessed. T2-weighted (w) fast spin echo, T1w gradient-echo and diffusion-weighted sequences were screened for the detectability of anatomical landmarks as listed below., Results: The interhemispheric fissure, ocular bulbs, corpus callosum, infundibulum, chiasm, septum pellucidum (SP), profile, and palate were detectable in 95%, 95%, 89%, 87%, 82%, 81%, 78%, 78% of cases. Olfactory tracts were more easily delineated than bulbs and sulci (37% versus 18% and 8%), with significantly higher detection rates in the coronal plane. The pituitary gland could be detected on T1w images in 60% with an increasing diameter with gestational age (p = 0.041). The delineation of olfactory tracts (coronal plane), chiasm, SP and pituitary gland were significantly increased after week 21 (p < 0.05). Pathologies were found in 28% of cases., Conclusion: This study provides detection rates for anatomical landmarks of forebrain development with fetal MRI before gw 27. Several anatomical structures are readily detectable with routine fetal MRI sequences; thus, if these landmarks are not delineable, it should raise the suspicion of a pathology. Recommendations regarding favorable sequences/planes are provided.
- Published
- 2010
- Full Text
- View/download PDF
23. Diagnostic pitfalls in fetal brain MRI.
- Author
-
Al-Mukhtar A, Kasprian G, Schmook MT, Brugger PC, and Prayer D
- Subjects
- Brain abnormalities, Brain embryology, Brain Diseases congenital, Female, Fetal Development, Humans, Pregnancy, Prenatal Diagnosis, Brain Diseases diagnosis, Diagnostic Errors, Fetal Diseases diagnosis, Magnetic Resonance Imaging
- Abstract
Recent technological advances in fetal magnetic resonance imaging (MRI) and increased reliability of MRI in depicting abnormalities and lesions, especially in the central nervous system, are increasingly bringing up challenging issues with regard to accurate diagnosis. There are also pitfalls not only attributable to image acquisition but also in clinical interpretation. The misinterpretation of findings because of insufficient knowledge about fetal brain development as visualized by MRI may also be regarded as an important limitation of fetal MRI. We provide an overview of the most common pitfalls experienced in fetal MRI in routine practice, demonstrate how to identify some of the factors that lead to imaging misinterpretation, and suggest ways to tackle these problems, with an emphasis on MR techniques and image calibration.
- Published
- 2009
- Full Text
- View/download PDF
24. Arterial embolization of unresectable hepatocellular carcinoma with use of microspheres, lipiodol, and cyanoacrylate.
- Author
-
Rand T, Loewe C, Schoder M, Schmook MT, Peck-Radosavljevic M, Kettenbach J, Wolf F, Schneider B, and Lammer J
- Subjects
- Embolization, Therapeutic adverse effects, Feasibility Studies, Female, Fluoroscopy, Follow-Up Studies, Humans, Male, Neoplasm Staging, Remission Induction, Retrospective Studies, Survival Rate, Tomography, X-Ray Computed, Treatment Outcome, Acrylic Resins therapeutic use, Carcinoma, Hepatocellular therapy, Cyanoacrylates therapeutic use, Embolization, Therapeutic methods, Gelatin therapeutic use, Hepatic Artery, Iodized Oil therapeutic use, Liver Neoplasms therapy, Tissue Adhesives therapeutic use
- Abstract
We performed a retrospective analysis of 46 patients with histologically confirmed hepatocellular carcinoma (HCC) who were treated with transarterial embolization (TAE) of the hepatic arteries. To induce permanent embolization, microspheres (Embosphere; 100 to 700 micron) and a mixture of ethiodized oil (Lipiodol Ultrafluide) with cyanoacrylate (Glubran) was injected. A total of 106 TAE procedures were performed. Cumulative survival rates were calculated. No patient died during embolization or within the first 24 hours. Severe procedure-related complications were observed in 2 patients. At the time of analysis, 38 of 46 patients were alive. The 180-, 360-, 520-, and 700-day cumulative survival rates for the total study population were 80.6%, 70.7%, 70.7%, and 47.1%, respectively, with a median survival of 666 days. TAE with the use of microspheres and Lipiodol and cyanoacrylate for unresectable HCC is a feasible treatment modality. Bland embolization with the use of microspheres can be used in patients for whom chemoembolization is not desired.
- Published
- 2005
- Full Text
- View/download PDF
25. Atypical focal nodular hyperplasia of the liver: imaging features of nonspecific and liver-specific MR contrast agents.
- Author
-
Ba-Ssalamah A, Schima W, Schmook MT, Linnau KF, Schibany N, Helbich T, Reimer P, Laengle F, Wrba F, Kurtaran A, Ryan M, and Mann FA
- Subjects
- Adult, Dextrans, Edetic Acid analogs & derivatives, Female, Ferrosoferric Oxide, Gadolinium DTPA, Humans, Iron, Liver pathology, Magnetite Nanoparticles, Male, Middle Aged, Oxides, Pyridoxal Phosphate analogs & derivatives, Retrospective Studies, Contrast Media, Focal Nodular Hyperplasia diagnosis, Magnetic Resonance Imaging
- Abstract
Objective: The objective of our study was to describe the functional and differential uptake features of atypical focal nodular hyperplasia using different MR contrast agents and to evaluate their potential role in the diagnosis and characterization of focal nodular hyperplasia., Materials and Methods: Contrast-enhanced MR images of 45 patients with 85 focal nodular hyperplasia lesions were retrospectively reviewed. In these patients, sonographic findings were nonspecific (n = 37), or CT features were inconclusive (n = 8). Non-liver specific gadolinium chelates were used in 18 patients (48 lesions) suspected of having either focal nodular hyperplasia or hemangioma. The following liver-specific agents were used in patients with suspected focal nodular hyperplasia or metastases: mangafodipir trisodium, 30 patients (55 lesions); ferumoxides, six patients (16 lesions); and SHU 555 A, six patients (six lesions). Individual lesions were quantified by signal intensity and assessed qualitatively by homogeneity, contrast enhancement, and presence of a central scar., Results: At unenhanced MR imaging, the triad of homogeneity, isointensity, and central scar was found in 22% of the focal nodular hyperplasia lesions. On mangafodipir trisodium-enhanced T1-weighted images, all focal nodular hyperplasia lesions showed contrast uptake: in 64% of the lesions, uptake was equal to parenchyma; 25%, greater than the parenchyma; and 11%, less than the parenchyma. On iron oxide-enhanced T2-weighted images, all focal nodular hyperplasia lesions showed uptake of the contrast agent, but contrast uptake in the lesions was less than in the surrounding parenchyma. Dynamic gadolinium chelate-enhanced MR imaging showed early and vigorous enhancement of focal nodular hyperplasia lesions with rapid washout in 88%. Atypical imaging features of the lesions included hyperintensity on T1-weighted images, necrosis and hemorrhage, and inhomogeneous or only minimal contrast uptake., Conclusion: For patients in whom the diagnosis of focal nodular hyperplasia cannot be established on unenhanced or gadolinium-enhanced MR imaging, homogeneous uptake of liver-specific contrast agent with better delineation of central scar may help to make a confident diagnosis of focal nodular hyperplasia.
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.